In the following discussion certain articles and processes will be described for background and introductory purposes. Nothing contained herein is to be construed as an “admission” of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and processes referenced herein do not constitute prior art under the applicable statutory provisions.
Recent advances in diagnostics have focused on less invasive mechanisms for determining disease risk, presence and prognosis. Diagnostic processes for determining genetic anomalies have become standard techniques for identifying specific diseases and disorders, as well as providing valuable information on disease source and treatment options.
Characterization of cell free nucleic acids in biological samples such as blood and plasma allows for less invasive techniques such as blood extraction to be used in making clinical decisions. For example, cell free DNA from malignant solid tumors has been found in the peripheral blood of cancer patients; individuals who have undergone organ transplantation have cell free DNA from the transplanted organ present in their bloodstream; and cell-free fetal DNA and RNA have been found in the blood and plasma of pregnant women. In addition, detection of nucleic acids from infectious organisms, such as viral or bacterial pathogens, provides important diagnostic and prognostic indicators.
However, the sensitivity of such testing is often dependent upon the identification of the amount of nucleic acid from the different sources, and in particular identification of a low level of nucleic acid from one source against a background of a much higher level of nucleic acids from a second source (e.g., fetal DNA in maternal plasma or viral nucleic acids in a patient sample). Determining the contribution of the minor nucleic acid species to the total nucleic acids present in the biological sample permits more accurate statistical interpretation of the resulting data.
In the case of copy number variants or aneuploidies, the portion of the chromosome with the copy number variant or the aneuploid chromosome may be genotypically identical to the background maternal DNA, hence fetal inheritance of an extra chromosome or portion thereof cannot be established merely by detecting the presence of nucleic acid sequences from the extra chromosome in the maternal sample.
There is thus a need for processes for calculating copy number variation (CNV) in one or more genomic regions in a biological sample using information on contribution of nucleic acids in the sample.